التفاصيل البيبلوغرافية
| العنوان: |
CRISPR genome-wide screening identifies PAK1 as a critical driver of ARSI cross-resistance in prostate cancer progression. |
| المؤلفون: |
Chen, Haojie1,2 (AUTHOR), Dong, Keqin1,3 (AUTHOR), Ding, Jie1 (AUTHOR), Xia, Jia1 (AUTHOR), Qu, Fajun1 (AUTHOR), Lan, Fuying2 (AUTHOR), Liao, Haihong1 (AUTHOR), Qian, Yuhang1 (AUTHOR), Huang, Jiacheng2 (AUTHOR), Xu, Zihan2 (AUTHOR), Gu, Zhengqin1 (AUTHOR) guzhengqin@xinhuamed.com.cn, Shi, Bowen1,4 (AUTHOR) shibowen2015@126.com, Yu, Mingming1,5 (AUTHOR) ymm2018@alumni.sjtu.edu.cn, Cui, Xingang1 (AUTHOR) cuixingang@xinhuamed.com.cn, Yu, Yongjiang1 (AUTHOR) yuyongjiang@xinhuamed.com.cn |
| المصدر: |
Cancer Letters. Apr2024, Vol. 587, pN.PAG-N.PAG. 1p. |
| مستخلص: |
Next-generation androgen receptor signaling inhibitors (ARSIs), such as enzalutamide (Enza) and darolutamide (Daro), are initially effective for the treatment of advanced prostate cancer (PCa) and castration-resistant prostate cancer (CRPC). However, patients often relapse and develop cross-resistance, which consequently makes drug resistance an inevitable cause of CRPC-related mortality. By conducting a comprehensive analysis of GEO datasets, CRISPR genome-wide screening results, ATAC-seq data, and RNA-seq data, we systemically identified PAK1 as a significant contributor to ARSI cross-resistance due to the activation of the PAK1/RELA/hnRNPA1/AR-V7 axis. Inhibition of PAK1 followed by suppression of NF-κB pathways and AR-V7 expression effectively overcomes ARSI cross-resistance. Our findings indicate that PAK1 represents a promising therapeutic target gene for the treatment of ARSI cross-resistant PCa patients in the clinic. PAK1 drives ARSI cross-resistance in prostate cancer progression. [Display omitted] • Advanced prostate cancer (PCa) often relapses and develops resistance to ARSIs. • PAK1 was identified as a significant contributor to ARSI cross-resistance in PCa. • Targeting PAK1 while using ARSI suppresses resistance progression. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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